Experimental autoimmune uveitis (EAU) is a well established model of human intraocular inflammatory diseases or uveitis and is easily induced in susceptible animal species by immunization with retinal proteins, such as interphotoreceptor retinoid binding protein (IRBP) and S-Antigen (SAg). Marked differences exist among different animal species and strains in their susceptibility to EAU induction but the cause for these differences is not completely clear. Mice are generally resistant to EAU while most rat strains are susceptible. Knowledge about the basic mechanisms underlying resistance to EAU or tolerance induction to ocular proteins may prove beneficial for the treatment or prevention of ocular inflammatory diseases. In FY1996, we showed that retinal autoantigens (SAg, IRBP, opsin, recoverin) and lens proteins (MIP, alphaA-crystallin, gamma-crystallin) are constitutively expressed in mouse thymus. In fiscal year 1997, we extended this analysis to other species; rats, monkeys and humans. Our results show for the first time a correlation between constitutive expression of ocular autoantigens in the thymus (mRNA and protein) and resistance to EAU. This correlation was noted both at the species (mice vs. rats or monkeys) and sub-species levels (differences among strains). The data thus provide a novel mechanistic explanation for the differences in susceptibility to autoimmune diseases, suggesting that resistance to an organ-specific autoimmune disease may be regulated at least in part by capacity to establish central tolerance to the relevant autoantigen.